Ionic liquid-catalyzed synthesis of triazoloquinazolinones, chromeno[4,3-d]benzothiazolopyrimidines and benzoimidazopyrimidine derivatives

Article abstract of DOI:10.1007/s11164-020-04151-6

1,3-Disulfonic acid imidazolium trifluoroacetate ([Dsim][CF₃CO₂]) was employed as an efficient, homogeneous and recyclable ionic liquid catalyst for the synthesis of triazoloquinazolinones, chromeno[4,3-d]benzothiazolopyrimidines and

Full text of DOI:10.1007/s11164-020-04151-6

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04151-6
Ionic liquid‑catalyzed synthesis of triazoloquinazolinones,
chromeno[4,3‑d]benzothiazolopyrimidines
and benzoimidazopyrimidine derivatives
Narjes Basirat1 · Seyed Sajad Sajadikhah1 · Abdolkarim Zare1
Received: 20 February 2020 / Accepted: 6 April 2020
© Springer Nature B.V. 2020
Abstract
1,3-Disulfonic acid imidazolium trifuoroacetate ([Dsim][CF3CO2]) was employed
as an efcient, homogeneous and recyclable ionic liquid catalyst for the synthesis of
triazoloquinazolinones, chromeno[4,3-d]benzothiazolopyrimidines and benzoimida-
zopyrimidine derivatives via one-pot multi-component reactions under thermal and
solvent-free conditions. The catalyst is demonstrated excellent catalytic properties
with good yields in short reaction times and low cost. All products were obtained by
recrystallization and there was no need to tedious work-up.
Keywords 1,3-disulfonic acid imidazolium trifuoroacetate ([Dsim][CF3CO2]) ·
Ionic liquid · Triazoloquinazolinone · Chromeno[4,3-d]benzothiazolopyrimidine ·
Benzoimidazopyrimidine
Introduction
Ionic liquids (ILs) are defned as molten salts with melting points below 100 °C
(273 K). In fact, ILs have a properties set of molten salts, ionic surfactants, ionic
crystals and molecular liquids. These properties challenge the classifcation of
ILs, which depends on whether the cation, anion and/or a functional group is
considered most important. Two most common IL types are protic and aprotic
ILs. Other classifcations of ILs include chiral, magnetic, polymeric, divalent,
fuorous, solvate, amino acid and aryl alkyl ILs [1]. Recently, ILs have attracted
much interests for types of chemical synthesis because of their unique properties
such as high polarity, low volatility, non-fammability, good solvating capability,
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04151-6) contains supplementary material, which is available to authorized users.
*
Seyed Sajad Sajadikhah
sssajadi@pnu.ac.ir
1
Department of Chemistry, Payame Noor University (PNU), P. O. Box, Tehran 19395-3697, Iran
Vol.:(0123456789)
1 3

N. Basirat et al.
wide liquid range, wide thermal stability, negligible vapor pressure, great selec-
tivity and recyclability [2–6]. Also, ILs have been used in many areas such as
separations and extractions [7], polymerizations [8], mass spectroscopy [9], elec-
trochemistry [10], plasticizers and electrolyte in batteries as solvents and cata-
lysts [11, 12]. Also, they have advantages such as combining of the properties
of the traditional liquid and solid acids, their practical simplicity, efciency and
selectivity. Many ILs have been reported as impressive catalysts in organic com-
pounds synthesis [13–23].
Multi-component reactions (MCRs) have been developed as a strong synthetic
tool in organic synthesis due to their advantages over the traditional multi-step
synthesis in which tri or more components simultaneously react together in one
reaction vessel to produce a desired product. MCRs are environmentally friendly,
economical, and they do not need expensive purifcation processes with minimum
time [24–30].
Five and six-membered heterocyclic compounds are valuable constituents which
frequently present in biologically active natural products and synthetic organic
compounds of medicinal and pharmaceutical interest [31, 32]. Among heterocy-
cles, quinazolinones and pyrimidine derivatives have attracted a major deal of con-
sideration [33, 34], because of their therapeutic and pharmacological attributes in
anti-HIV [35], muscle relaxant [36], neuroleptic [37], hypnotic [38], antihistaminic
[39], anticancer [40, 41]. There are many studies that they have employed various
catalysts for the synthesis of triazoloquinazolinone and fused pyrimidine deriva-
tives via MCRs, such as sulfamic acid [24], nano-SiO2 [26], H6P2W18O62·18H2O
[42], molecular iodine [43], acetic acid [44], ionic liquids [45–47], sodium lauryl
sulphate (SLS) micelles [48], hydrotalcite [49], VB1 [50], Zn(ClO4)2·6H2O [51],
NS–C4(DABCO–SO3H)2·4Cl [52], [PVPH]ClO4 [53] and [bmim+][BF4−] [54].
With this explanation, in this work, we reported the synthesis of triazolo-
quinazolinones, chromeno[4,3-d]benzothiazolopyrimidines and benzoimidazo-
pyrimidine derivatives via one-pot multi-component reactions in the presence of
1,3-disulfonic acid imidazolium trifuoroacetate ([Dsim][CF3CO2]) as an efcient
and homogeneous ionic liquid catalyst (Scheme 1).
Experimental
All chemicals used in this work were purchased from Merck or Fluka and used with-
out any subsequent purifcation. FT-IR spectra were obtained by a FT-IR spectrom-
eter (Tensor 27 Bruker) at room temperature in the range of 400–4000 cm−1. Melt-
ing points were measured on an Electrothermal 9100 apparatus. NMR spectra were
recorded with a Bruker DRX-400 and DRX-500 AVANCE instrument (400 and
500 MHz for 1H, 100 and 125 MHz for 13C) in DMSO-d6 as solvent. Mass spectrum
of the catalyst was recorded on a Finnigan MAT 8430 mass spectrometer operating
at an ionization potential of 70 eV. Thin layer chromatography (TLC) was obtained
from 60 GF254 silica gel sheets from the German chemical company.
1 3

Ionic liquid-catalyzed synthesis of triazoloquinazolinones,…
R
N
O
O
NH2
CHO
+
[Dsim][CF3CO2] (3 mol%)
Solvent-free, 50 °C
N
N
N
HN
+
N
O
R
N
H
1
3
2
4
S
OH
N
O
N
O
CHO
+
[Dsim][CF3CO2] (3 mol%)
Solvent-free, 50 °C
S
N
+
O
NH2
O
R
6
1
5
R
7
R
CHO
+
H
N
O
O
O
[Dsim][CF3CO2] (10 mol%)
MeOH, reflux
+
NH2
OEt
N
OEt
N
R
8
1
9
N
N
H
10
N
N
[Dsim][CF3CO2]:
CF3CO2
SO3H
HO3S
Scheme 1 Synthesis of triazoloquinazolinones 4, chromeno[4,3-d]benzothiazolopyrimidines 7 and ben-
zoimidazopyrimidine derivatives 10 in the presence of [Dsim][CF3CO2]
Procedure for the preparation of ionic liquid 1, 3‑disulfonic acid imidazolium
chloride ([Dsim]Cl−)
At frst, to a solution of imidazole (5 mmol) in CH2Cl2 (50 mL), chlorosulfonic
acid (10.2 mmol) was added dropwise over a period of 30 min at room tempera-
ture under vigorous stirring. After the addition was completed, the reaction mix-
ture was stirred for 12 h under pressure of nitrogen (to remove the produced HCl),
stand for 10 min, and the CH2Cl2 was decanted. The residue was washed with dry
CH2Cl2 (3 × 50 mL) and dried under vacuum to give [Dsim]Cl− as a viscous yel-
low oil.
Procedure for the preparation of ionic liquid 1,3‑disulfonic acid imidazolium
trifuoroacetate ([Dsim][CF3CO2])
To a round-bottomed fask (50 mL) containing [Dsim]Cl− (5 mmol) was added
trifuoroacetic acid (10.5 mL) dropwise over a period of 20 min at room tempera-
ture under vigorous stirring. After the completion addition, the reaction mixture
was stirred for 6 h under vacuum to remove the extra methylsulfonate. Obtained
ionic liquid is 1,3-disulfonic acid imidazolium trifuoroacetate ([Dsim][CF3CO2])
[55]; FT-IR (KBr): 3600–2400 (OH), 1730, 1646, 1588, 1310, 1226, 1175, 1052,
1
882, 852 cm−1; H NMR (500 MHz, DMSO-d6): δ = 14.37 (2H, s, 2OH), 9.07
1 3

N. Basirat et al.
(1H, s, Ar), 7.67 (2H, s, Ar) ppm; 13C NMR (125 MHz, DMSO-d6): δ = 158.7,
134.7, 119.7, 119.0 ppm.
General procedure for the synthesis of triazoloquinazolinones 4
A mixture of aldehyde 1 (1 mmol), dimedone 2 (1 mmol) and 3-amino-1,2,4-tria-
zole 3 (1 mmol) in the presence of [Dsim][CF3CO2] (3 mol%) was stirred at 50 °C
for the appropriate time. After completion, the reaction mixture was cooled to room
temperature and deionized water (10 mL) was added. To obtain crude product, the
mixture was fltered, separated and washed twice with deionized water (2×5 mL).
The recrystallization process was carried out in ethanol to obtaining purred solid
product. All products were identifed by comparison of their physical data and prop-
erties with those known reported compounds.
6,7-Dihydro-9-phenyl-6,6-dimethyl-[1,2,4]triazolo[5,1-b]quinazolin-
8(4H,5H,9H)-one (4a) (Table 2, entry 1): 1H NMR (400 MHz, DMSO-d6): δ=11.06
(1H, s, NH), 7.80 (1H, s, Ar), 7.17–7.05 (5H, m, Ar), 6.05 (1H, s, CH), 2.71–2.63
(2H, m, CH2), 2.21 (1H, d, J=8.3 Hz, CH2), 2.12 (1H, d, J=8.3 Hz, CH2), 1.13
(3H, s, CH3), 0.92 (3H, s, CH3) ppm; 13C NMR (100 MHz, DMSO-d6): δ=192.1,
154.5, 149.3, 145.0, 142.1, 130.8, 128.3, 108.2, 57.4, 51.3, 48.5, 29.3, 25.0 ppm.
6,7-Dihydro-6,6-dimethyl-9-p-tolyl-[1,2,4]triazolo[5,1-b]quinazolin-
8(4H,5H,9H)-one (4b) (Table 2, entry 2): 1H NMR (400 MHz, DMSO-d6): δ=11.05
(1H, s, NH), 7.70 (1H, s, Ar), 7.03 (4H, s, Ar), 6.09 (1H, s, CH), 2.70–2.62 (2H,
m, CH2), 2.38 (3H, s, CH3), 2.24 (1H, d, J=5.7 Hz, CH2), 2.17 (1H, d, J=5.7 Hz,
CH2), 1.11 (3H, s, CH3), 0.98 (3H, s, CH3) ppm; 13C NMR(100 MHz, DMSO-d6):
δ=192.9, 154.5, 149.0, 144.1, 143.6, 129.9, 128.6, 126.0, 108.1, 57.2, 51.6, 48.5,
29.2, 24.8, 22.3 ppm.
6,7-Dihydro-6,6-dimethyl-9-(4-chlorophenyl)-[1,2,4]triazolo[5,1-b]quinazolin-
8(4H,5H,9H)-one (4e) (Table 2, entry 5): 1H NMR (400 MHz, DMSO-d6): δ=11.20
(1H, s, NH), 7.28 (1H, s, Ar), 7.44 (2H, d, J=7.4 Hz, Ar), 7.35 (2H, d, J=7.4 Hz,
Ar), 6.20 (1H, s, CH), 2.40–2.31 (2H, m, CH2), 2.20 (1H, d, J=6.0 Hz, CH2), 2.00
(1H, d, J=6.0 Hz, CH2), 1.14 (3H, s, CH3), 0.90 (3H, s, CH3) ppm; 13C NMR
(100 MHz, DMSO-d6): δ=190.2, 155.4, 149.0, 146.3, 142.2, 135.3, 130.2, 128.0,
111.9, 50.1, 48.5, 47.1, 26.1, 25.7 ppm.
General procedure for the synthesis of chromeno[4,3‑d]
benzothiazolopyrimidines 7
A mixture of arylaldehyde 1 (1 mmol), 4-hydroxycoumarin 5 (1 mmol), 2-amin-
obenzothiazole 6 (1 mmol) and 3 mol% of [Dsim][CF3CO2] was stirred in an oil
bath at 50 °C. After the reaction was completed, as observed by TLC, the reaction
mixture was washed with hot water to separate [Dsim][CF3CO2] and fltered product
dried at ambient temperature. Afterward, to obtain pure product, precipitation was
recrystallized in hot ethanol.
7-Phenylchromeno[4,3-d]benzothiazolo[3,2-a]pyrimidin-6(7H)-one
(7a)
(Table 3, entry 1): 1H NMR (400 MHz, DMSO-d6): δ=7.47–7.36 (4H, m,
1 3

Ionic liquid-catalyzed synthesis of triazoloquinazolinones,…
Ar), 7.24–7.17 (5H, m, Ar), 7.06–7.00 (4H, m, Ar), 6.27 (1H, s, CH) ppm; 13C
NMR(100 MHz, DMSO-d6): δ=170.3, 168.8, 164.8, 160.8, 146.3, 145.6, 135.6,
134.5, 133.8, 131.2, 130.4, 128.8, 127.6, 126.5, 123.8, 122.5, 117.8, 117.5, 116.3,
105.8, 88.5 ppm.
7-(4-Nitrophenyl)chromeno[4,3-d]benzothiazolo[3,2-a]pyrimidin-6(7H)-one (7i)
(Table 3, entry 9): 1H NMR (400 MHz, DMSO-d6): δ=8.17 (2 H, d, J=6.7 Hz, Ar),
7.78 (2 H, d, J=6.4 Hz, Ar), 7.52 (2H, t, J=5.8 Hz, Ar), 7.33 (2H, q, J=5.8 Hz,
Ar), 7.20–7.25 (4H, m, Ar), 6.14 (1H, s, CH) ppm; 13C NMR (100 MHz, DMSO-
d6): δ=170.4, 168.1, 163.6, 156.0, 144.8, 135.9, 133.0, 132.6, 129.6, 129.4, 128.8,
128.3, 127.6, 127.3, 127.1, 125.2, 123.3, 121.9, 121.2, 107.2, 82.4 ppm.
7-(4-Chlorophenyl)chromeno[4,3-d]benzothiazolo[3,2-a]pyrimidin-6(7H)-one
(7l) (Table 3, entry 12): 1H NMR (400 MHz, DMSO-d6): δ=7.86 (2H, d, J=9.5 Hz,
Ar), 7.77 (2H, d, J=9.5 Hz, Ar), 7.48–7.42 (4H, m, Ar), 7.29 (1H, t, J=6.0 Hz,
Ar), 7.19 (1H, d, J=6.7 Hz, Ar), 7.10–7.06 (2H, m, Ar), 6.33 (1H, s, CH) ppm; 13
C
NMR (100 MHz, DMSO-d6): δ=172.6, 168.8, 163.4, 159.6, 145.7, 144.1, 136.8,
136.0, 135.2, 133.3, 130.5, 129.7, 129.0, 128.7, 127.6, 126.5, 125.6, 112.1, 104.6,
81.9 ppm.
General procedure for the preparation of benzo[4,5]imidazo[1,2‑a]pyrimidines 10
Aldehyde 1 (1 mmol), ethyl acetoacetate 8 (1 mmol), 2-aminobenzoimidazole 9
(1 mmol) and [Dsim][CF3CO2] (10 mol%) were added to methanol. The reaction
mixture was stirred under refux conditions and its progress followed by TLC. After
completion, the reaction mixture was cooled to ambient temperature and solvent was
evaporated. The residual was washed with warm water to separate the ionic liquid
catalyst and recrystallized in hot ethanol to give pure product 10.
Ethyl 2-methyl-4-phenyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-car-
boxylate (10a) (Table 6, entry 1): 1H NMR (400 MHz, DMSO-d6): δ=10.67 (1H, s,
NH), 7.49–7.42 (2H, m, Ar), 7.31 (2H, t, J=4.7 Hz, Ar), 7.11 (2H, t, J=6.5 Hz, Ar),
6.91 (3H, t, J=4.7 Hz, Ar), 6.35 (1H, s, CH), 4.19 (2H, q, J=5.6 Hz, OCH2CH3),
2.45 (3H, s, CH3), 1.28 (3H, t, J=5.6 Hz, OCH2CH3) ppm; 13C NMR(100 MHz,
DMSO-d6): δ=165.6, 147.1, 144.0, 133.0, 132.9, 130.0, 129.8, 129.1, 128.5, 126.3,
126.0, 121.3, 119.6, 108.8, 57.2, 45.7, 18.0, 14.4 ppm.
Ethyl
4-(4-nitrophenyl)-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrim-
1
idine-3-carboxylate (10c) (Table 6, entry 3): H NMR (400 MHz, DMSO-d6):
δ=10.79 (1H, s, NH), 8.11 (2H, d, J=6.5 Hz, Ar), 7.74 (2H, d, J=6.5 Hz, Ar),
7.39 (1H, d, J=6.5 Hz, Ar), 7.28 (1H, d, J=6.5 Hz, Ar), 7.17–6.95 (2H, m, Ar),
6.62 (1H, s, CH), 4.04 (2H, q, J=6.5 Hz, OCH2CH3), 2.49 (3H, s, CH3), 1.30 (3H,
t, J=6.5 Hz, OCH2CH3) ppm; 13C NMR(100 MHz, DMSO-d6): δ=166.4, 148.9,
143.8, 135.7, 134.0, 130.1, 129.8, 128.5, 127.7, 126.5, 122.6, 120.3, 118.0, 109.7,
59.8, 55.6, 21.2, 16.0 ppm.
Ethyl 4-(4-chlorophenyl)-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrim-
1
idine-3-carboxylate (10e) (Table 6, entry 5): H NMR (400 MHz, DMSO-d6):
δ=10.65 (1H, s, NH), 7.57–7.49 (3H, m, Ar), 7.31 (2H, d, J=5.1 Hz, Ar), 7.19
(2H, d, J=7.1 Hz, Ar), 7.06 (1H, d, J=5.1 Hz, Ar), 6.40 (1H, s, CH), 4.08 (2H,
1 3

N. Basirat et al.
Table 1 Optimization of
reaction conditions for the
synthesis of 4a under solvent-
free conditions
Entry
Catalyst
(mol%)
Temperature Time (min)
(°C)
Yield (%)a
1
2
3
4
5
6
2
3
4
2
3
4
25
25
25
50
50
50
45
45
40
22
15
20
40
45
50
90
98
99
aIsolated yield
Table 2 Synthesis of triazoloquinazolinones 4
R
N
O
O
NH2
CHO
+
[Dsim][CF3CO2] (3 mol%)
Solvent-free, 50 °C
N
N
N
HN
+
N
O
R
N
H
1
3
2
4
Entry
R
H
Product
Time (min)
Yield (%)a
M.p. (°C)
Found
Reported
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
15
25
30
5
5
35
98
97
97
99
98
92
98
245–247
260–263
295–297
293–295
299–300
298–300
260–263
248–250 [45–47]
264–269 [45–47]
>300 [26]
4-Me
4-OMe
4-NO2
4-Cl
4-OH
3-NO2
>300 [26]
307–309 [43]
304–306 [44]
266–269 [24]
4g
5
aIsolated yield
q, J=5.0 Hz, OCH2CH3), 2.35 (3H, s, CH3), 1.44 (3H, t, J=5.0 Hz, OCH2CH3)
ppm; 13C NMR(100 MHz, DMSO-d6): δ=164.2, 147.5, 146.0, 138.6, 134.1, 132.0,
131.8, 130.0, 129.8, 125.2, 122.2, 120.0, 111.4, 95.5, 57.7, 52.1, 21.3, 15.6 ppm.
Results and discussion
First, to optimize the amounts of the catalyst and reaction conditions, the solvent-
free reaction of benzaldehyde (1 mmol), dimedone (1 mmol) and 3-amino-1,2,4-tri-
azole (1 mmol) in the presence of diferent amounts of [Dsim][CF3CO2] as catalyst
1 3

Ionic liquid-catalyzed synthesis of triazoloquinazolinones,…
O
S
O
CF3CHO2
N
N
HO3S
O
H
H
O
O
2
H
1
R
O
R
[Dsim][CF3CO2]
O2CCF3
O
H
R
O
N
OH
O
S
N
H
N
H
O
N
N
HO3S
O
O
4
-H2O
R
R
O2CCF3
O
O
H
O
H
N
N
N
A
N
N
O
N
H
NH
R
O
S
O
CF3CO2
C
H
O
S
O
H
N
N
CF3CO2
H
O
SO3H
N
N
HO3S
O
O
H
N
N
N
O
NH
B
O
S
H
N
N
O
SO3H
O
Scheme 2 Plausible mechanism for the preparation of 4
Table 3 Efect of diferent
Entry
Catalyst
(mol%)
Temperature Time (h)
(°C)
Yield (%)a
amounts of catalyst and various
temperatures on the synthesis
of 7c
1
2
3
4
5
6
2
3
4
2
3
4
25
25
25
50
50
50
10
8
7
4
2.5
29
43
58
85
94
95
2.5
Reaction conditions: 4-hydroxycoumarin (1 mmol), 4-methoxyben-
zaldehyde (1 mmol) and 2-aminobenzothiazole (1 mmol) under sol-
vent-free conditions
aIsolated yield
1 3

N. Basirat et al.
was examined. The reaction was carried out with 2, 3 and 4 mol% of catalyst at
room temperature and 50 °C. As it is shown in Table 1, 3 mol % of [Dsim][CF3CO2]
at 50 °C aforded 9-phenyl-6,6-dimethyl-5,6,7,9-tetrahydro-4H-1,2,4-triazolo[5,1-b]
quinazolin-8-one 4a in 15 min with 98% of yield as the best result (Table 1, entry 5).
Following, three-component condensation reaction of the aromatic aldehydes
1, dimedone 2 and 3-amino-1,2,4-triazole 3 under optimum conditions was stud-
ied to synthesis of the triazoloquinazolinone derivatives 4a–g (Table 2). The wide
ranges of substituted diferent aldehydes with their corresponding products synthe-
sized in good to high yields using the ionic liquid [Dsim][CF3CO2]. The presence
of electron-donating groups on the aromatic aldehydes aforded the corresponding
products in moderate yields, and the reaction was sluggish; however, the presence
of electron-withdrawing groups aforded the corresponding products in shorter reac-
tion times with higher yields.
The proposed mechanism for the reaction using [Dsim][CF3CO2] for the prep-
aration of 4 from benzaldehyde 1, dimedone 2 and 3-amino-1,2,4-triazole 3 is
described in Scheme 2. According to studies reports [24, 26, 45–47], 2-benzylidene-
5,5-dimethylcyclohexane-1,3-dione A, containing the electron-poor C–C double
bond, is formed quantitatively by Knoevenagel condensation between benzaldehyde
1 and dimedone 2 in the presence of [Dsim][CF3CO2]. Then, subsequent Michael-
type addition of 3-amino-1,2,4-triazole 3 to A gave intermediate B. The intermedi-
ate B was cyclized by the nucleophilic attack of NH group on the C=O moiety and
gave the intermediate C. Finally, the corresponding product 4 was generated by the
elimination of H2O.
Motivated from the above results in the synthesis of triazoloquinazolinones,
the catalytic activity of [Dsim][CF3CO2] was examined for the preparation of
chromeno[4,3-d]benzothiazolopyrimidine derivatives 7 (Scheme 1). At frst, for
optimization of the amounts of the catalyst and reactions conditions, the solvent-free
reaction of 4-hydroxycoumarin (1 mmol), 4-methoxybenzaldehyde (1 mmol) and
2-aminobenzothiazole (1 mmol) was performed in the presence of diferent amounts
of [Dsim][CF3CO2] at room temperature as well as 50 °C. As it is shown in Table 4,
3 mol% of [Dsim][CF3CO2] at 50 °C aforded 7-(4-methoxyphenyl)chromeno[4,3-d]
benzothiazolo[3,2-a]pyrimidin-6(7H)-one 7c in 2.5 h with 94% yield (Table 3, entry
5).
Next, the substrate scope of the reaction was evaluated using a variety of structur-
ally diverse aldehydes. Aromatic aldehydes produced the products 7 in high yields.
The presence of electron-withdrawing groups on the aromatic aldehydes aforded
the desired products in moderate yields, and the reaction was sluggish; however, the
presence of electron-donating groups aforded the corresponding products in shorter
reaction times with high yields (Table 4).
According to reported literature [49], in the beginning, mechanism involves the
Knoevenagel condensation of the 4-hydroxycoumarin 5 and aldehyde 1 in the pres-
ence of [Dsim][CF3CO2] to giving intermediate E. This is followed by Michael
addition of 2-aminobenzothiazole 6 to the C=C bond of intermediate E and formed
intermediates F. Then, an intramolecular cyclic condensation between amino and
carbonyl groups of the Michael adduct F occurs to aford intermediate G and then
H, which aford the desired compound 7 by dehydration (Scheme 3).
1 3

Ionic liquid-catalyzed synthesis of triazoloquinazolinones,…
Table 4 Synthesis of chromeno[4,3-d]benzothiazolopyrimidines 7a–m
S
OH
N
O
N
O
CHO
+
[Dsim][CF3CO2] (3 mol%)
Solvent-free, 50 °C
S
N
+
O
NH2
O
R
6
1
5
R
7
Entry
R
H
Product
Time (h)
Yield (%)a
M.p. (°C)
Found
Reported
1
2
3
4
5
6
7
8
7a
7b
7c
7d
7e
7f
7g
7h
7i
2.5
2.5
2.5
2.5
3
3
2.5
2
3
3
3
3
91
93
94
94
87
87
93
95
88
89
85
85
86
200–201
262–264
231–235
245–248
229–231
213–216
248–251
278–281
292–295
262–266
265–267
194–197
241–244
200–202 [49]
264–267 [49]
236–239 [49]
249–252 [49]
232–235 [48]
216–219 [48]
248–251 [48]
281–282 [48]
296–298 [48]
266–269 [48]
268–272 [48]
198–202 [48]
247–250 [48]
4-OEt
4-OMe
3-OMe
2-Cl
2-Br
4-Me
4-OH
4-NO2
3-NO2
4-CN
4-Cl
9
10
11
12
13
7j
7k
7l
4-Br
7m
3
aIsolated yield
O
S
O
O
S
O
N
R
O
HO3S
N
S
H
O
N
N
O
O
SO3H
HN
O
CF3CO2
H
H
N
O
H
O
R
N
S
-H2O
O
O
O
O
O
NH
1
R
E
F
5
H
6
O
S
O
H
O2CCF3
N
N
HO3S
O
O
[Dsim][CF3CO2]
HO3S
CF3CO2
N
N
S
S
O
O
S
S
H
H
N
O
N
O
N
N
N
O
N
O
HO
HO
H
O
O
R
O
2 C
R
R
H
G
7
C
F
3
Scheme 3 Reaction mechanism for the synthesis of compound 7
1 3

N. Basirat et al.
Table 5 Optimization of the
reaction conditions for the
synthesis of 10a
Entry Catalyst Conditions
(mol%)
Time (min) Yield (%)a
1
2
3
4
5
6
7
8
10
10
5
15
10
10
15
10
MeOH, rt
EtOH, rt
MeOH, rt
MeOH, rt
MeOH, 45 °C
MeOH, refux
MeOH, refux
Solvent-free, 80 °C
100
100
120
100
75
20
20
30
50
38
Trace
52
80
95
96
64
aIsolated yield
Table 6 Synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines 10a–h
R
O
CHO
+
H
N
O
O
[Dsim][CF3CO2 ](10 mol%)
MeOH, reflux
+
NH2
OEt
N
OEt
N
R
8
1
9
N
N
H
10
Entry
R
H
Product
Time (min)
Yield (%)a
M.p. (°C)
Found
Reported
1
2
3
4
5
6
7
8
10a
10b
10c
10d
10e
10f
20
35
20
20
25
15
45
15
95
96
95
91
93
91
76
95
275–277
261–263
>300
250–252
295–297
266–268
258–260
>300
280–282 [52]
258–260 [53]
300–302 [53]
256–258 [53]
297–300 [52]
263–265 [52]
261.6–261.7 [50]
307–309 [53]
4-Me
4-NO2
4-OMe
4-Cl
3-Cl
4-OH
10g
10h
4-CN
aIsolated yield
In another efort, our attention was focused on the application of [Dsim][CF3CO2]
for the synthesis of benzoimidazopyrimidine derivatives 10. One-pot three-compo-
nent reaction of benzaldehyde (1 mmol), 2-aminobenzoimidazole (1 mmol) and
ethyl acetoacetate (1 mmol) was carried out in the presence of [Dsim][CF3CO2]
(10 mol%) under diferent conditions (Table 5). The best result was obtained by
10 mol% of the catalyst in methanol under refux conditions (Table 5, entry 6).
The optimized conditions were used for the condensation of 2-aminobenzo-
imidazole and ethyl acetoacetate with diferent aromatic aldehydes to exhibit the
1 3

Ionic liquid-catalyzed synthesis of triazoloquinazolinones,…
efciency and the generality of this method (Table 6). Aldehydes containing both
electron-withdrawing and electron-donating substituents react gently to aford the
desired benzo[4,5]imidazo[1,2-a]pyrimidine derivatives 10a–h in good to high
yields within relatively short reaction times.
The proposed mechanism for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimi-
dines 10 is described in Scheme 4 [52, 53]. Initial condensation between aldehyde 1
and ethyl acetoacetate 8 aforded intermediate K. The addition of 2-aminobenzoimi-
dazole 9 to intermediate K leads to intermediate L, which converted to intermediate
M through cyclization reaction. Eventually, benzo[4,5]imidazo[1,2-a]pyrimidines
10 were obtained by elimination of water in the presence of [Dsim][CF3CO2].
To exhibit the availability and applicability of the presented work, it can be
compared with several reported results in the literature. The results demonstrated
that the present work can be useful for preparation of triazoloquinazolinones
4, chromeno[4,3-d]benzothiazolo[3,2-a]pyrimidin-6(7H)-one 8 and benzo[4,5]
imidazo[1,2-a]pyrimidines 10 (Table 7).
Conclusions
In summary, 1,3-disulfonic acid imidazolium trifuoroacetate ([Dsim][CF3CO2])
was used as an efective, homogeneous ionic liquid catalyst for the synthesis of tria-
zoloquinazolinones, chromeno[4,3-d]benzothiazolopyrimidines and benzoimida-
zopyrimidine derivatives via one-pot multi-component reactions. There are several
advantages for these methods such as good efciency, generality and high yields of
O
S
O
O
S
O
N
N
R
HO3S
O
O
H
N
N
HO3S
H
O
H
O
S
O
N
N
O
O
HO3S
O
H
O
O
H
O
O
CF3CO2
OEt
N
1
OEt
OEt
H
H
-H2O
J
8
K
CF3CO2
R
H2N
CF3CO2
N
H
3
R
H
R
[Dsim][CF3CO2]
F
9
C
C
2
O
O
O
OEt
N
OEt
OH
N
N
-H2O
N
N
H
O
NH
M
H
CF3CO2
L
H
R
O
S
O
H
O
S
O
N
N
O
N
N
HO3S
O
HO3S
O
OEt
N
N
10
N
H
Scheme 4 Proposed mechanism for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidines 10
1 3

N. Basirat et al.
Table 7 Comparison of the results of [Dsim][CF3CO2] with other catalysts in the synthesis of com-
pounds 4a, 7a and 10a
Compound Conditions
Time
Yield (%) [Ref.]
4a
NH2SO3H (0.05 mmol), CH3CN, 80 °C
Acetic acid (5 mL), 60 °C
30 min 95 [24]
25 min 95 [26]
Iodine (10 mol%), CH3CN, refux
[Dsim][CF3CO2] (3 mol%), solvent-free, 50 °C
SLS (10 mol%), H2O, rt
Hydrotalcite (0.08 g), solvent-free, 70 °C
[Dsim][CF3CO2] (3 mol%), solvent-free, 50 °C
10 min 84 [43]
20 min 98 (Present work)
7a
5 h
91 [48]
2 h
95 [49]
2.5 h
91 (Present work)
10a
NS–C4(DABCO–SO3H)2·4Cl (20 mg), solvent-free, 90 °C 30 min 91 [52]
[PVPH]ClO4 (30 mg), solvent-free, 100 °C
VB1 (5 mol%), H2O, refux
45 min 92 [53]
3 h
6 h
90 [50]
83 [54]
[bmim+][BF4−] (3 mL), 90 °C
[Dsim][CF3CO2]− (10 mol%), MeOH, refux
20 min 95 (Present work)
the reaction products, short reaction times, safety, clean reaction profle, easy han-
dling, non-volatility and economical of the catalyst. Additionally, all products were
obtained through simple fltration and there was no need for column chromatogra-
phy, which reduces the waste as well as environmental pollutions.
Acknowledgements We thank the Research Council of Payame Noor University for providing the neces-
sary research facilities and the fnancial support of this work.
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